Objective To explore whether there is a causal relationship between intestinal flora and esophageal cancer. Methods Summary statistics of intestinal flora and esophageal cancer were obtained from the Genome-wide Association Studies (GWAS) database. Five methods, including inverse variance weighted (IVW), weighted median estimation, Mendelian randomization (MR)-Egger regression, single mode, and weighted mode, were used for analysis, with IVW as the main analysis method. Sensitivity analysis was used to evaluate the reliability of MR results. Results In the IVW method, Oxalobacteraceae [OR=1.001, 95%CI (1.000, 1.002), P=0.023], Faecalibacterium [OR=1.001, 95%CI (1.000, 1.002), P=0.028], Senegalimassilia [OR=1.002, 95%CI (1.000, 1.003), P=0.006] and Veillonella [OR=1.001, 95%CI (1.000, 1.002), P=0.018] were positively correlated with esophageal cancer, while Burkholderiales [OR=0.999, 95%CI (0.998, 1.000), P=0.002], Eubacterium oxidoreducens [OR=0.998, 95%CI (0.997, 0.999), P=0.038], Romboutsia [OR=0.999, 95%CI (0.998, 1.000), P=0.048] and Turicibacter [OR=0.998, 95%CI (0.997, 0.999), P=0.013] were negatively correlated with esophageal cancer. Sensitivity analysis showed no evidence of heterogeneity, horizontal pleiotropy and reverse causality. Conclusion Oxalobacteraceae, Faecalibacterium, Senegalimassilia and Veillonella increase the risk of esophageal cancer, while Burkholderiales, Eubacterium oxidoreducens, Romboutsia and Turicibacter decrease the risk of esophageal cancer. Further studies are needed to explore how these bacteria affect the progression of esophageal cancer.

Objective To analyze the relationship between neuroticism and gastroesophageal reflux disease (GERD) using the Mendelian randomization (MR) method. Methods Exposure and outcome data were downloaded from the Integrative Epidemiology Unit (IEU) database in August 2023, including summary statistics from genome-wide association studies (GWAS) for neuroticism (n=374 323) and GERD (n=602 604). MR was conducted using the weighted median method, MR-Egger method, inverse variance weighted method, weighted mode method, and simple mode method. The causal relationship between the two was assessed using odds ratio (OR), and sensitivity analyses were performed to ensure the accuracy of the results. Results Neuroticism was associated with an increased risk of GERD [OR=1.229, 95%CI (1.186, 1.274), P<0.001]. Similarly, GERD was associated with an increased risk of neuroticism [OR=1.786, 95%CI (1.623, 1.965), P<0.001]. Conclusion There is a bidirectional causal relationship between neuroticism and gastroesophageal reflux disease.

OBJECTIVE: To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD. METHODS: A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot. RESULTS: Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01). CONCLUSION Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals ; Electroacupuncture ; Dementia, Vascular/genetics* ; Male ; Rats ; Signal Transduction ; Humans ; Memory ; Rats, Sprague-Dawley ; Nuclear Receptor Coactivators/genetics* ; Ferritins/genetics* ; Learning ; Hippocampus/metabolism* ; Acupuncture Points

The rationale for the design of control groups in tuina clinical trial is the foundation for rigorously validating the effectiveness and safety of this therapy. This article reviewed the current state of the design of tuina placebo in control groups of clinical trials， pointed out the necessity of setting up tuina placebo in clinical trials of tuina， analyzed the challenges in implementing blinding of tuina manipulation， and concluded that tuina placebo is still challenged by the placebo effect， the diversification of tuina manipulation but the lack of standardization， and the difficulty of implementing blinding due to the high level of public awareness of tuina. This article also summarized the design of placebo manipulation in three types of clinical trials， including spinal manipulation， acupressure， and paediatric tuina， and proposed four strategies for designing placebo tuina manipulation-controlling placebo effects， developing operational standards for placebo tuina manipulation， ensuring the rigor of blinding implementation， and applying new technologies to enhance the standardization and blinding capacity of placebo tuina methods. So the article is aimed at improving the methodological quality of tuina clinical trial designs， and promoting the standardization and scientificity of tuina clinical trial design.

Objective:To construct a dual performance management model based on data envelopment analysis (DEA),so as to assess the quality of metrological management of medical equipment,and formulate management countermeasures. Methods:The dual performance management model was constructed by adopting data envelopment analysis-banker-charnes-cooper (DEA-BCC). The evaluation indicator system was built from two dimensionalities included input performance and output performance,which can perform comprehensive evaluation meterring performance of equipment,so as to formulate three dimensional measure included improvement of management team,optimization of metrological process,and routine monitor and management for improving metrological management of equipment. A total of 183 used medical equipment of International Peace Maternity & Child Health Hospital of China welfare institute (IPMCH) from 2022 to 2023 were selected. The metrological management of 176 medical equipment from January to December 2022 adopted formulation of management countermeasures on the basis of subjective evaluation to perform management (subjective evaluation),and the metrological management of 177 medical equipment (included 170 equipment that were used in subjective evaluation) from January to December 2023 adopted formulation of management countermeasures on the basis of dual performance evaluation (dual performance evaluation). The self-made online survey questionnaire was used to investigate the recognition degree of 104 operators of clinical department,who used the equipment. Among of them,48 operators received the management method of subjective evaluation,and 56 operators received the dual performance evaluation. The metrological management performance,management effectiveness and clinical recognition degree of the two kinds of management methods for medical equipment were compared. Results:The values of standardized input performance,output performance and comprehensive performance of equipment,which adopted dual performance evaluation management,were respectively 87.74±3.61,97.19±1.70 and 1.11±0.04. Input performance of dual performance evaluation management was lower than that of subjective evaluation management method,and output performance and comprehensive performance of dual performance evaluation management were higher than these of subjective evaluation management method,and the differences of them between two methods were statistically significant (t=4.866,4.457,7.793,P<0.05). The average metrological pass rates of mechanics,thermodynamics,thermology,textiles and medical equipment of medical laboratory of using dual performance evaluation management were (97.99±1.14)％,(97.39±2.08)％,(97.43±1.87)％,(98.06±0.92)％ and (96.77±2.03)％,respectively. All of them were higher than these of using subjective evaluation management method,and the differences of them between two methods were statistically significant (t=4.431,3.232,3.324,4.928,3.352,P<0.05). The satisfaction rates of 56 operators of equipment,who adopted dual performance evaluation management,were respectively 98.21％,94.64％,96.43％,100.00％ and 98.21％ for the management system,metrological frequency,metrological items,metrological effect and service quality of metrological staffs of equipment,which were higher than these of subjective evaluation management method,and the differences of them between two methods were statistically significant (x2=7.240,5.660,6.296,6.128,12.735,P<0.05). Conclusion:The dual performance management model can control the input of metrological management of medical equipment,and enhance the output of metrological management of medical equipment,and promote the operation quality of medical equipment,and improve the level of clinical service of medical equipment.

AIM:To investigate the potential mechanisms by which cell division cycle protein 42(Cdc42)regulates endothelial-mesenchymal transition(EndMT)in pulmonary hypertension(PH).METHODS:The pulmonary hypertension(PH)model was established using Sugen-5416 combined with hypoxia.Twenty-four C57BL/6 mice were ran-domly divided into four groups:normoxia control(CON)group,normoxia+ML141(CON+ML141)group,Sugen-5416+hypoxia(SuHx)group,and SuHx+ML141 group,with 6 mice in each group.After 4 weeks,right ventricular systolic pressure(RVSP)and cardiac ultrasound parameters were measured,and lung tissues were collected for immunofluores-cence staining.Pulmonary microvascular endothelial cells(PMVECs)were isolated using magnetic bead sorting.Calcium imaging was performed to assess Ca2+signaling,and Western blot was used to detect EndMT-related proteins as well as stromal interaction molecule 1(STIM1)and Orai1 expression.RESULTS:In the SuHx group,mice exhibited signifi-cantly increased RVSP,Fulton index(right ventricle/left ventricle+septum),end-diastolic right ventricular free wall thick-ness(RVEDWT),and end-systolic right ventricular free wall thickness(RVESWT)(P<0.01).Conversely,pulmonary artery acceleration time/pulmonary artery ejection time(PAT/PET)and tricuspid annulus plane systolic excursion(TAPSE)were significantly reduced(P<0.01).The Cdc42 inhibitor ML141 ameliorated these changes.The SuHx group exhibited a significant decrease in CD31 fluorescence intensity in pulmonary vascular endothelial cells(P<0.01),a marked increase in α-smooth muscle actin(α-SMA)fluorescence intensity in smooth muscle cells(P<0.01),and the emergence of CD31/α-SMA co-localization.These alterations were reversed by ML141.Hypoxia induced EndMT in PM-VECs,characterized by decreased CD31 and vascular endothelial cadherin(VE-cadherin)along with increased α-SMA and vimentin(P<0.01),which was suppressed by ML141(P<0.01).Hypoxia activated store-operated calcium entry(SOCE),enhancing intracellular Ca2? release,extracellular Ca2? influx,and basal Ca2? levels(P<0.01),while upregulat-ing STIM1 and Orai1 expression(P<0.01).These changes were reversed by ML141.Furthermore,both ML141 and STIM1 knockdown inhibited the upregulation of EndMT-related transcription factors Snail and Twist(P<0.05).CON-CLUSION:Cdc42 may participate in EndMT in PH by regulating store-operated calcium channels in pulmonary microvas-cular endothelial cells.

BACKGROUND:Intertrochanteric femoral fractures are the main type of fragility fracture in the elderly,and proximal femoral nail antirotation is the preferred surgical option,but the factors associated with postoperative internal fixation failure are controversial.OBJECTIVE:A new"three-column"classification of intertrochanteric femoral fractures was proposed by evaluating patients'imaging data preoperatively and analyzing its interaction with postoperative internal fixation failure.A risk prediction model was developed and validated by using numerical algorithms,which facilitates clinicians to identify and intervene in high-risk patients preoperatively.METHODS:Patients with intertrochanteric femur fractures in Sanshui Branch of Foshan Hospital of Traditional Chinese Medicine between June 2012 and June 2022 were selected.The patients were divided into the internal fixation failure group and the internal fixation maintenance group according to whether they had internal fixation failure after surgery.According to the preoperative radiographs,the proximal femur was divided into three columns:the medial column,the lateral column,and the middle column.Each column had different subgroups.The relationship between the morphological characteristics of the"three columns"and the failure of proximal femoral nail antirotation internal fixation was analyzed,and the independent risk factors for internal fixation failure were screened out by single and then multifactorial logistic regression analyses.A risk prediction model was constructed according to the independent risk factors using R language software.The Bootstrap method was used to resample 1 000 times.The area under the curve,calibration curve,and clinical decision curve were used to evaluate the differentiation,calibration ability,and clinical application value of the model.The Youden index was used to determine the optimal risk cut-off value of the prediction model,according to which the patients were divided into high and low risk groups.The stability and extensibility of the model were evaluated according to the accuracy of its risk prediction ability.RESULTS AND CONCLUSION:(1)The four independent risk factors for postoperative internal fixation failure after surgery were predicted using the"three-column"typing system:medial column(comminuted fracture of the lesser trochanter and femoral talar)[odds ratio=5.385,95％CI(1.961,14.782),P=0.001],medial column(chimney type)[odds ratio=2.893,95％CI(1.167,7.173),P=0.022],lateral column(lateral wall thickness＜20.5 mm)[odds ratio=2.804,95％CI(1.078,7.297),P=0.035]and lateral column(lateral wall fracture)[odds ratio=4.278,95％CI(1.670,10.959),P=0.012].(2)The constructed risk prediction model showed good discrimination and accuracy[area under the receiver operating characteristic curve=0.852,95％CI(0.837,0.922)].The calibration curve showed good agreement between the model-predicted risk and the actual risk of occurrence.(3)The clinical decision curve suggested that the model had good clinical applicability when the risk threshold probability was in the range of 0.2-0.82.The risk probability of 28％was the optimal threshold for risk stratification of the model,and the predictive performance of the model was better in patients with different risk groups.(4)The"three-column"typing system constructs a predictive model to calculate the risk probability of postoperative internal fixation failure in patients with intertrochanteric femoral fractures.This method is accurate,simple,and easy to apply clinically,and can be used as a digital tool to guide personalized clinical treatment.

Objective:To observe and analyze the abnormal gait characteristics and lower limb kinematic chain in patients with bilateral moderate-to-severe hallux valgus(HV)during adaptive walking.Method:From September 2022 to August 2023,33 patients with moderate-and-severe HV were selected from the department of arthrology,Wangjing Hospital,Chinese Academy of Traditional Chinese Medicine and en-rolled in the observation group.A group of 29 healthy subjects were matched and enrolled in the control group.DC-G-150-F2 three-dimensional gait analysis system was used to collect gait characteristics and lower limb motion chain of two groups during a 10m adaptive walking test.Temporal-spatial gait parameters and ki-nematic changes in the hip,knee,and ankle joints were observed and analyzed.Result:The gait time-space parameters of left and right support phase,total double support phase,left lateral foot deviation angle,step length,stride length and pace in the observation group were significantly lower than those in the control group(P＜0.05).In contrast,the time-space parameters of left and right swing phase and stride frequency in the observation group were significantly higher than those in the control group(P＜0.05).The two groups had no significant difference in right lateral foot deviation angle and step width(P＞0.05).The range of flexion and extension of the right hip joint,rotation of the left hip joint,rotation of the left and right knee joint and flexion and extension of the left and right ankle joint in the observation group were significantly lower than those in the control group(P＜0.05).There were no significant differences be-tween the two groups in the range of motion of left hip flexion and extension,right hip rotation,left versus right hip spreading,left versus right knee flexion and extension,and left versus right ankle rotation(P＞0.05).However,the range of motion of right hip rotation and right knee flexion and extension was lower than that of the control subjects(P=0.084,P=0.093).Conclusion:Gait changes in patients with bilateral moderate-to-severe bunions are characterized by shortened sin-gle and double support phases,prolonged swing phase,increased step frequency,reduced step length and stride length,and a"broken stride and slow catching up"walking pattern.The range of motion of each lower limb joint in the sagittal plane and horizontal plane is reduced,resulting in a rigid and twisted state through-out the lower limb kinematic chain.

Background and Aims:Laparoscopic hiatal hernia repair(LHHR)is the gold-standard surgical treatment for hiatal hernia(HH),but postoperative recurrence remains a challenge due to hiatal enlargement and disruption of the phrenoesophageal ligament.This study aimed to assess the feasibility,safety,and short-term efficacy of a novel three-dimensional small intestinal submucosa(3D-SIS)patch designed for circumferential crural reinforcement and ligament-like reconstruction in a porcine LHHR model.Methods:Twelve healthy pigs(35-40 kg)were equally randomized into non-mesh group,SIS flat patch group,and 3D-SIS patch group.All animals underwent LHHR and Nissen fundoplication under general anesthesia.In the non-mesh group,the hiatal defect was closed with interrupted sutures.In the SIS flat patch group,a U-shaped SIS patch was placed posterior to the esophagus to reinforce the crura and fixed with medical glue.In the 3D-SIS patch group,an intraoperatively assembled three-dimensional patch was applied,consisting of an upper keyhole-shaped layer for circumferential diaphragmatic reinforcement,a tubular middle part encircling the abdominal esophagus,and a lower small keyhole-shaped patch covering the gastroesophageal junction,all fixed with medical glue.After 3 months,laparotomy was performed to assess recurrence,patch integration,and complications,followed by biomechanical and histological evaluations.Results:All procedures were completed successfully with no deaths or major complications.Operative time was slightly longer in the patch groups,while blood loss was similar.No hernia recurrence or patch migration was observed at 3 months.Biomechanical testing revealed higher ultimate load and Young's modulus in both SIS groups than in the non-mesh group.Histological analysis demonstrated neovascularization and collagen deposition in the patch groups,with the 3D-SIS patch showing more complete circumferential integration and ligament-like tissue formation.Conclusion:The 3D-SIS patch is feasible and safe in porcine LHHR.It provides circumferential diaphragmatic reinforcement and promotes phrenoesophageal ligament-like regeneration,offering a new concept for reducing postoperative recurrence and reconstructing the anti-reflux barrier.